We have previously reported that the ligation of three monocyte surface antigens, by their specific immobilized antibodies, induces the release of IL-1 and TNF from human monocytes. The results of this work were published in Science 249:1295-97, 1990. We are currently investigating whether one of these surface antigens, CD44, is involved in the binding of endotoxin to human monocytes. We have observed that one hour after the addition of endotoxin to human monocytes, the expression of CD44, but not several other surface antigens, is lowered by approximately 25%. In addition, we have found an anti-CD44 antibody which is able to block the endotoxin induced TNF release from monocytes. This inhibition of TNF release may be the result of competitive binding between the antibody and endotoxin. To determine if CD44 is one of the binding proteins for endotoxin, we plan to carry out crosslinking studies using radiolabeled endotoxin. We will then determine if the receptor-endotoxin complexes can be immunoprecipitated by antibodies to CD44.